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Background: Secondary syphilis is a sexually transmitted infection, which is referred to as "the great imitator" and has a wide spectrum of clinical manifestations. As a result, it is essential to identify potential secondary syphilis patients with ambiguous clinical manifestation through pathology., Objective: We sought to analyze the pathological features of secondary syphilis., Methods: We analyzed 59 biopsy specimens from 56 patients with secondary syphilis. Cases were classified according to the histological characteristics and clinical features., Results: Necrotic keratinocytes could be observed in 39 of 59 (66.1%) secondary specimens. Plasma cells (86.4%) were the most common finding overall. The presence of Treponema pallidum was detected mostly at the dermal-epidermal junction. There was no statistical significance between pathological features and age, HIV status, or RPR titer., Conclusions: Necrotic keratinocytes are one of the characteristics of secondary syphilis. The combination of plasma cells, irregular acanthosis, elongated rete ridges, and endothelial swelling should increase the likelihood of syphilis., (© 2019 S. Karger AG, Basel.)

We have explored the rash that appears as target lesions, with the central and dominant diseases belonging to the Stevens-Johnson syndrome/toxic epidermal necrolysis group. After presenting the clinical patterns of an individual target lesion and classifying them into different types of lesions, the contribution has been organized with groups characterized by such specific findings according to the type of lesion: flat or raised, typical or atypical, presence or absence of fever, presence or absence of mucosal ulcerations, presence or absence of arthralgias, and/or internal organ involvement. Other specific features, such as histologic appearance, immunofluorescence findings, and laboratory changes, are considered. We provide clinicians with an algorithmic, systematic, and logical approach to diagnose the condition of the patients who present with targetoid lesions, and enable them to differentiate between those with serious systemic and life-threatening diseases from others with ordinary skin ailments., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The number of cases of syphilis continues to rise in the UK, USA and elsewhere and may present to a variety of clinical specialties. We report a complex case of early acquired disseminated syphilis causing an ulceronodular rash (lues maligna), orchitis, osteitis and lung nodules in an immunocompetent man who has sex with men who presented to the genitourinary medicine clinic. Syphilis should be considered in the differential diagnoses of multiple clinical presentations and optimal management should involve multidisciplinary care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Although syphilis is uncommon, infection rates are much higher in HIV-infected individuals than the general population. A proposed explanation is impaired cellular immunity with HIV infection., Methods: A search of one institution yielded 10 patients with a diagnosis of secondary syphilis on skin biopsy, positive syphilis serology and available CD4 counts. We evaluated 11 biopsies from the 10 patients. We correlated the patients' CD4 counts with the histologic findings and with the number of treponemes on skin biopsies, highlighted by immunohistochemistry (IHC). We also compared the detection of spirochetes in silver stained sections (e.g. Warthin-Starry) with T. pallidum IHC. All biopsies were assessed for various histologic features., Results: The sensitivity of IHC to detect treponemes was 64% and of silver stain was 9% (p-value 0.04). The number of treponemes on the biopsies was determined by IHC. High numbers of spirochetes (i.e. >100 per 10 hpf) were only seen in patients with CD4 counts less than 250 cells/ml., Conclusion: The most consistent histologic finding was a moderate to severe lymphoplasmacytic infiltrate. Although the study is small, it appears that a higher number of spirochetes is associated with CD4 counts less than 250 cell/ml. The T. pallidum IHC stain was vastly superior to the Warthin-Starry stain., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Early malignant syphilis is a rare and severe variant of secondary syphilis. It is clinically characterized by lesions, which can suppurate and be accompanied by systemic symptoms such as high fever, asthenia, myalgia, and torpor state. We report a diabetic patient with characteristic features of the disease showing favorable evolution of the lesions after appropriate treatment.

A previously healthy 24-year-old man presented with an erythematous, non-pruritic and painless papulonodular skin rash affecting the trunk, upper arms (excluding palms), neck, face, forehead and scalp. He had a penile ulcer for the past 2 weeks, almost healed at the time of observation. The patient tested positive for syphilis and HIV-1; he claimed being negative for HIV 6 months earlier. As the palms were not affected, we performed a skin biopsy for the differential diagnosis between secondary lues and acute HIV seroconversion reaction. Benzathine penicillin (2,400,000 units) was administrated and antiretroviral therapy started. Although the skin biopsy was compatible with secondary syphilis, there was no change in the skin rash 3 weeks after the first penicillin administration. Another 2 doses of penicillin were given but 4 weeks later the rash persisted. A second biopsy revealed a mucinous skin infiltration, compatible with nodular mucinosis., (2015 BMJ Publishing Group Ltd.)

A 62-year-old male presented with a 10-day history of a diffuse, erythematous papular rash sparing the palms and soles. Histopathologic examination of a skin lesion showed loose non-caseating granulomas in a lymphoplasmacytic background. Scattered spirochetes were identified by Treponema pallidum immunohistochemistry, in keeping with a diagnosis of secondary syphilis. Granulomatous inflammation in secondary syphilis is uncommon. A review of the literature reveals that the majority of prior reported cases of granulomatous secondary syphilis share similar characteristics to this case; namely, a papular or nodular clinical presentation, sparing of the palms and soles, and collections of epithelioid histiocytes with associated lymphocytes and variable numbers of plasma cells., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We report the case of a 21-year-old woman with symmetrically distributed, ulcerated nodules and plaques on the face, neck and arms. Initial differential diagnoses included pyoderma or sarcoidosis based on the clinical presentation and histopathology with non-caseating granulomas. After inefficient treatment with topical and systemic fusidic acid and steroids, we diagnosed nodular secondary syphilis owing to positive serology and immunohistochemical staining of Treponema pallidum in lesional skin. After treatment with benzathine penicillin, skin lesions improved and antibody titres declined significantly within 3 months. Nodular skin lesions in secondary syphilis are rare with 15 reported cases within the last 20 years. Furthermore, the granulomatous histology is often misleading. Our patient's case suggests that the physicians should be aware of syphilis as a possible differential diagnosis also in patients outside a high-risk population for sexually transmitted diseases and with an unusual clinical presentation.

There are limited reports on the ultrastructure of syphilis skin lesions. The aim of this study has been to perform an electron microscopic investigation of the morphology and the tissue distribution of treponemes in primary and secondary cutaneous lesions. Three cases of primary syphilitic chancre and one case of secondary syphilis were included. Prominent epidermal abnormalities in the primary chancre and a perivascular inflammatory infiltrate in the secondary lesion were found by light microscopy. Ultrastructurally, spirochetes were located mainly in the blood vessel walls and dermal tissue of the chancre lesions. In the secondary syphilis case, spirochetes were more abundant between epidermal keratinocytes. Most of them adjusted to the intercellular spaces. Occasionally, the electron microscopy images were highly suggestive of an intracellular location. Both the ultrastructural and immunohistochemical examination of the primary and secondary syphilis lesions showed a paradoxical distribution of the causative microorganisms compared to the light microscopic changes. In addition, the ultrastructural findings strongly suggest that Treponema pallidum subspecies pallidum invades tissues, not only through an intercellular, but also through a transcellular pathway.

There are diverse skin manifestations of both leprosy and syphilis. These diseases can appear similar to many other dermatologic conditions as well as to systemic diseases with dermatologic signs. Nodular syphilis is an uncommon type of secondary syphilis. We present here a person from a leprosy-endemic area with diffuse nodular skin lesions of secondary syphilis who was initially suspected of having lepromatous leprosy.

According to WHO, syphilis represents 3% of all sexually transmitted diseases. Additionally, the occurence of this disease has also been increasing in developed countries. The secondary stage of syphilis is characterized by a large variety of symptoms and may mimic many skin diseases. The generalized exanthem of the secondary stage is often confused with a drug eruption. The systemic involvement may also resemble other diseases. It is due to these peculiarities that syphilis, and in particular its secondary stage, is known in literature as the "clinical chameleon" or "great imitator". Nonspecific neurological symptoms like headache, lightheadedness, and slight mental depression appear prior to the skin manifestations characteristic of the second stage of the disease. Subsequently, when the patient begins to develop the characteristic disseminated maculopapular exanthem with palmoplantar involvement, the clinician may have to re-evaluate to exclude an early form of syphilitic meningoencephalitis. We report here the case of a female patient with suspected endogenous depression as part of the post-climacterium syndrome. Shortly after the introduction of antidepressant therapy the patient developed a generalized maculopapular exanthem. She was seen in the Dermatology clinic due to suspicion for a drug eruption. A diagnosis of secondary syphilis with palmoplantar involvement, associated with an early form of syphilitic meningoencephalitis, was established. After systemic antibiotic treatment, complete remission was achieved.

Background: Secondary syphilis, which typically begins 4-10 weeks after initial exposure to Treponema pallidum, manifests with a range of cutaneous patterns. One unusual variation features oval, targetoid plaques that may resemble erythema multiforme (EM)., Methods: We describe a 23-year-old woman with an EM-like eruption, a mucous patch, and a prominent alopecia somewhat moth-eaten in appearance. She had positive rapid plasma reagin and fluorescent treponemal antibody absorption (FTA-ABS) tests, and a skin biopsy revealed swollen endothelial cells with a superficial perivascular infiltrate containing plasma cells. Response to intramuscular penicillin therapy was consistent with the empiric diagnosis of secondary syphilis., Conclusions: One should consider secondary syphilis in the differential diagnosis of an eruption resembling EM., (© 2010 The International Society of Dermatology.)

Background: In 1952, Zoon described a series of patients with dense plasma-cell infiltrates in the glans penis. Since then, similar Zoon-like lesions (ZLL) have been described on the external female genitalia and in the airways, for which over 20 designations currently exist., Methods: Twenty-eight cases of ZLL, twenty-two cases of lichen planus, eight cases of plasmacytoma and two cases of syphilis were evaluated from the surgical pathology archive at the University of Virginia. Twenty-four histologic data points were tabulated in each case, including 12 epidermal and 12 dermal features., Results: Histopathologic findings were similar in the majority of cases of ZLL, regardless of their location. They demonstrated superficial cutaneous erosions, basal vacuolar alteration and many showed lozenge-shaped keratinocytes in the epiderms. The dermis contained a dense inflammatory infiltrate composed predominantly of plasma cells, with scattered neutrophils and lymphocytes. Dense fibrosis was seen in the upper dermis., Conclusions: A uniform nomenclature for ZLL does not exist. Based on the results of this analysis, we suggest that the generic term idiopathic lymphoplasmacellular mucositis-dermatitis be considered to encompass the lymphoplasmacellular infiltrates in the skin and mucosal surfaces considered herein. This designation is morphologically descriptive and can be applied regardless of anatomic location.

We have recently shown that a monoclonal antibody, designated M131, that binds a surface phosphorylcholine epitope on Treponema pallidum possesses complement-dependent killing activity and confers partial protection in rabbits following passive immunization (Blanco et al., 2005, Infect. Immun. 73:3083-3095). In this study, the protective potential of M131 was further tested using the rabbit skin protection assay of Titus and Weiser. Both M131 and infection-derived immune rabbit serum resulted in significant lesion delays corresponding to at least a 90% reduction of the treponemal challenge inoculum. The skin protection assay provides a way to assess the protective potential of specific immunogens while using far less antibody than in passive immunization protocols.

Two mild syphilis cases are hereby described. Their clinical and morphological characteristics differ. The first case showed syphilitic gums on the right eyebrow rim and tuberous lesions, some of which ulcerated. They made up plaques like archs on limbs. The second case showed nodular lesions distribute on practically all the cutaneous tegument. The specific and non-specific syphilitic tests were positive. The CRL study on the cellular and serological aspects was normal. The histopathologic pieces were compatible with the clinical diagnosis. Lesions evolved to a quick disappearance with the penicillin G benzatine treatment established. Attention is drawn to the possibility of noticing new cases of mild syphilis due to the present high incidence of the sexually transmitted diseases.

Electron microscopical studies of primary syphilitic lesions showed intensive changes in the capillaries in the form of endothelial proliferation and extensive infilitration of different cells in the surrounding connective tissue. The degenerative changes in axon terminals could explain the painless course of primary induration.

Filamentous aggregates of collagen are distinct structures in the pathological dermis. These aggregates are distinguishable from fibrous long-spacing collagen (in vitro and at biopsy) and the Luse body. The aggregates are produced from dermal collagen fibrils by clostridial collagenase and culture-medium extract, which supposedly contains cellular collagenase at a neutral pH, as well as by organ cultures. In vitro experiments showed that carrageenan granuloma contains fibrous long-spacing collagen and segment long-spacing collagen. The granuloma also contains the aggregates. The aggregates were found in skin biopsies from syphilitic chancres, acrosclerotic scleroderma, morphea, mycosis fungoides, myeloid leukemia, mastocytosis and malignant melanoma. These findings indicate that the aggregates are products of the in situ degradation of collagen fibrils by some collagenolytic factor. This factor may originate in fibroblast-like cells, reticulum cells, leukemia cells, mast cells and melanoma cells.

Histology of ulcus durum with regional simple lymphadenitis and of condyloma latum was presented. Inflammatory lymphoplasmocytic infiltration included eosinophilic leukocytes in both cases. Syphilitic granulomatous lymphadenitis with conspicuous productive perilymphadenitis has been lasting about 1 month. Treponemas in histological section were found only in condyloma latum.

An immunohistological study of skin biopsy specimens from patients with early syphilis was undertaken before and after treatment (one day after intramuscular administration of 2.4 MIU benzathine penicillin and eight days later, after a total administration of 3.6 MIU. In chancres from seronegative patients treatment with 3.6 MIU usually resulted in fewer immunocompetent cells in the infiltrate. In lesions of secondary syphilis treatment with 2.4 MIU benzathine penicillin produced a significant decrease in immunocompetent cells. After treatment with 3.6 MIU there was no further decrease. It was worth noticing that even eight to nine days after the initial pretreatment biopsy, when 3.6 MIU had been administered, the overall lymphohistiocytic infiltrate was not substantially diminished. Significantly more suppressor (T8+) cells were found in lesions of primary syphilis than of secondary syphilis, and they showed remarkable exocytosis. Activated local T8+ cells may release immunosuppressive lymphokines.

This paper reports a case of malignant syphilis (man, 39 years old) in whom ultrastructural investigations of a typical nodule revealed an extremely low amount of bacteria with the characteristics of Treponema pallidum in poorly differentiated cells of the dermal infiltrate with plasma cells, stimulated lymphocytes, and neutrophils as predominating cell types. Most of the microorganisms bore signs of disintegration. Vascular changes and exocytosis were only demonstrable by light microscopy in a second nodule. Together with the high production rate of immunoglobulins and an excessive inflammatory reaction, these findings point to an aberrant biologic reaction pattern of those patients who develop malignant syphilis. Unfortunately, further investigations concerning a possible impairment of cellular immunity as supposed in the literature, had not been possible in the present case.

The alterations of early syphilitic infection occuring in the course of high dosage penicillin (120 mega IU, 36 h) as clinical experimental trial has been studied both from the clinical and the electron microscopical views. By electron microscopical studies, findings revealing the localization and the status of treponemes before and during penicillin treatment could be established. Before treatment started, the majority of treponemes was of intercellular localization. In the course of treatment various forms of destruction could be differentiated. The most striking change in the host tissue after 7-8 h of penicillin therapy was an elimination of treponemes by penetrating phagocytes. 24 h after the beginning of treatment, treponemes could not be demonstrated any more. The clinical and serological findings after the high dosage penicilline will produce results comparable to those of conventional therapie.

Syphilis is still a common disease in many countries. The clinical features of secondary syphilis are well documented, and the histopathological features of secondary syphilis have been reviewed in a few studies. The present study documents the histopathology of secondary syphilis based on 68 skin biopsies from 38 patients. Based on the findings of this study, and a review of the literature, diagnostic guidelines are suggested and the differential diagnoses are discussed.